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The purpose of this research study is to determine if the addition of dutasteride to a regimen with abiraterone acetate and prednisone will improve on therapy in patients with castrate-resistant prostate cancer and metastatic disease. This study will also help determine the side effects of the study treatment and how often they occur.

Condition or disease

Intervention/treatment

Phase

Prostate Cancer

Drug: Abiraterone acetateDrug: DutasterideDrug: Prednisone

Phase 2

Detailed Description:

Patients will receive abiraterone acetate and prednisone orally, once daily for 2 months (2 cycles) on an outpatient basis. At the start of cycle 3, dutasteride will be taken once daily. Patients will return to the clinic on Day 14 of the first 3 cycles for routine blood tests.

Patients will come to the clinic every 12 weeks for a CT scan and/or x-ray of the chest, CT scan or MRI of the abdomen and pelvis, bone scan, and blood test for testosterone and other specialized blood test.

Abiraterone acetate 1000mg orally once per day + prednisone 5mg orally once per day for two months, followed by abiraterone 1000mg orally once per day + prednisone 5mg orally once per day + dutasteride 3.5mg orally once per day in 28-day cycles until symptomatic or radiographic progression

Number of Participants With Androgen Receptor (AR) Related Mutations [ Time Frame: Pairs of patients samples were evaluated at baseline and time of progression. In this study cohort, participants were followed up to 48 months for this endpoint. ]

AR related mutation was defined as presence of T878A mutation. Expression of T878A was measured by established methods.

Secondary Outcome Measures
:

Change in Serum Levels of Testosterone [ Time Frame: Samples for testosterone analyses were obtained at baseline and at time of progression. In this study cohort, participants were followed up to 48 months for this endpoint. ]

Serum testosterone levels were estimated based on established methods. The change from baseline to progression was calculated for each participant.

Prostate-Specific Antigen (PSA) Response [ Time Frame: PSA was measured at baseline and day 1 of every cycle on treatment. In this study cohort, participants were followed up to 48 months for this endpoint. ]

PSA response was defined as decline of 50% from baseline confirmed by a PSA at least 4 weeks later based on Prostate-specific Antigen Working Group-2 (PSAWG-2) (2008) criteria.

Time to PSA Progression [ Time Frame: PSA was measured at baseline and day 1 of every cycle on treatment. In this study cohort, participants were followed up to 48 months for this endpoint. ]

Time to PSA progression based on the Kaplan-Meier method was defined as the time between registration and documented PSA progression. PSA progression based on Prostate-Specific Antigen Working Group-2 (PSAWG-2) (2008) criteria was an increase of >/=25% and >/= 2 ng/ml after 12 weeks for patients without a PSA decline from baseline and an increase of >/=25% and >/= 2 ng/ml above the nadir, confirmed by a 2nd value 3 weeks or later for patients with a PSA decline from baseline. PSA progression was reported not duration of response.

Best Overall Response [ Time Frame: Disease was evaluated radiologically at baseline and every 12 weeks cycles on treatment. In this study cohort, participants were followed up to 48 months for this endpoint. ]

Overall response (OR) rate was defined as achieving partial response (PR) or complete response (CR) based on RECIST 1.0 criteria on treatment. Per RECIST 1.0 for target lesions, CR is complete disappearance of all target lesions and PR is at least a 30% decrease in the sum of longest diameter (LD) of target lesions, taking as reference baseline sum LD. To be assigned a status of CR or PR, changes in tumor measurements must be confirmed by repeat assessments performed no fewer than 4 weeks after the response criteria are first met. PR or better overall response assumes at a minimum incomplete response/stable disease (SD) for the evaluation of non-target lesions and absence of new lesions.

Time to Progression (TTP) [ Time Frame: Disease evaluation occurred every 12 weeks while patients were receiving treatment. In this study cohort, participants were followed up to 48 months for this endpoint. ]

TTP based on the Kaplan-Meier method is defined as the duration of time from study entry to documented first observation of progressive disease (PD). Per RECIST 1.0 for target lesions, PD is at least a 20% increase in sum LD of target lesions, taking as reference the smallest sum LD recorded since the treatment started or appearance of new lesions. For non-target lesions, PD is the appearance of one or more new lesions and/or unequivocal progression of existing non-target lesions.

Presence of AR Amplification [ Time Frame: Patients' samples were evaluated at baseline and every 12 weeks on treatment. In this study cohort, participants were followed up to 48 months for this endpoint. ]

Presence of AR amplification was measured by established methods.

Change in Serum Androgen Levels [ Time Frame: Pairs of patients' samples for androgen analyses were obtained at baseline and at time of progression. In this study cohort, participants were followed up to 48 months for this endpoint. ]

Serum androgen levels measured based on established methods. The change from baseline to progression was calculated for each participant.

Change in Circulating Tumor Cells (CTCs) Levels [ Time Frame: Pairs of patients' samples were evaluated at baseline and time of progression. In this study cohort, participants were followed up to 48 months for this endpoint. ]

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Ages Eligible for Study:

18 Years and older (Adult, Senior)

Sexes Eligible for Study:

Male

Accepts Healthy Volunteers:

No

Criteria

Inclusion Criteria:

Diagnosis of adenocarcinoma of the prostate

Castrate resistant disease

Metastatic disease

Normal organ and marrow function

Subjects with partners of childbearing potential must be willing to use adequate methods of birth control

Exclusion Criteria:

Uncontrolled intercurrent illness

Uncontrolled hypertension

Active or symptomatic viral hepatitis or chronic liver disease

History of pituitary or adrenal dysfunction

Clinically significant heart disease

History of a different malignancy unless disease-free for at least 5 years

Known brain metastasis

History of gastrointestinal disorders

Prior therapy with abiraterone acetate

HIV-positive individuals on antiretroviral therapy

Requirement for steroid use greater than the equivalent of 5 mg of prednisone daily